Acute haemolysis and appearance of PNH-like clones in patients with vitamin B12 deficiency and iron deficiency after iron dextran administration
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1 Acute haemolysis and appearance of PNH-like clones in patients with vitamin B12 deficiency and iron deficiency after iron dextran administration Chun-Liang Lin 1, Chin-Chan Lin 1,Wen-Jyi Lo 2,Yu-Chien Chang 2,Chang-Fang Chiu 1 1.Division of Haematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 2.Stem Cell Research Laboratory and Tissue Bank, CMUH, Taiwan
2 Present illness A 29-year-old woman Presented with to dyspena for two weeks She had received ileum resection at the age of seven -suppurative appendicitis
3 Course1 Hb MCV WBC PLT ferritin vitamin B12 (mecobolamin) 7.0 g/dl 68.6 fl 5200 ul 313,000 ul 1.8 ng/ml <50 pg/ml after IV iron supplementation of two weeks dyspnea worsened
4 Course1 Re-check of data Hb 5.8 g/dl MCV 91.7 fl WBC 2580 ul PLT 149,000 ul reticulocytes 0.66 % total bilirubin 1.63 mg/dl direct bilirubin 0.29mg/dl LDH 2868 U/L haptoglobin <5 mg/dl Direct and indirect Coomb s tests (-)
5 Peripheral blood smear macrocytic anemia with anisocytosis, poikilocytosis.
6 Bone marrow examination hypercellularity, (cellularity: 90-95%) with megaloblastoid change. The M/E ratio is markedly increased due to proliferation of mature and immature myeloid cells with dispersed erythroid. cytogenetic studies revealed 46XX in the analysis of 25 cells.
7 Differential diagnosis Coombs negative hemolytic anemia Drugs Toxins Microangiopathic hemolytic anemia infections Membrane disorders: Paroxysmal nocturnal hemoglobinuria Liver disease
8 Peripheral blood sampling Flow cytometric evaluation population of FLAER-deficient granulocytes 7.6% population of CD59-deficient 9.6% RBC Blood, Charles Parker,
9 PNH-like clones (Before vit B12 treatment) Before Control Before RBC WBC
10 Course2 One week - mecobolamin was administrated reticulocytes 13.79% Two weeks - mecobolamin supplementation haemoglobin 7.7 g/dl MCV 68.4 fl Four weeks - mecobolamin supplementation Flow cytometric evaluation population of FLAER-deficient granulocytes 0% population of CD59-deficient RBC 2.2%
11 PNH-like clones (After vit B12 treatment) After After RBC WBC WBC
12 Course3 Intravenous iron dextran was re-challenged- no haemolysis 3 months after vitamin B12 and iron supplementation haemoglobin 11 g/dl the patient was in health status.
13 Discussion
14 Vitamin B12 deficiency and RBC destruction Intramedullary destruction is well understand. But intravascular haemolysis in advance anemia is rare.
15 Mechanism of RBC destruction 1. Abnormalities of erythrocyte membrane proteins, ex: spectrin. 2. Severe hyperhomocysteinemia caused by vitamin B12 deficiency and MTHFR(methylenetetrahydrofolate reductase) gene mutations and vitamin B12 deficiency possibly related to peripheral blood hemolysis. Journal of hematology & oncology, Acharya U.2008;1:26 Journal of clinical investigation 1978, Ballas SK,61,
16 7% PNH-like clones in our vitamin B12 deficiency of patient PIG-A mutant blood cells are in the blood and bone marrow of healthy person %. Aplastic anemia and myelodysplastic syndromes also harbor small populations less than 1%. Haematol,Jeffrey J, Nephrology,dialysis,transplantation,Buus NH 2007,22,661-2
17 PNH and acute hemolysis Precipitating factor: infection surgery transfusions iron supplementation vaccination menstruation Wintrobe s clinical hematology, 12 edition, Vygovskaia.1982;27:39-42
18 PNH and acute hemolysis The haemolysis after iron supplement probably - outpouring of a cohort of young erythrocytes, a larger proportion of which is more complement sensitive than those in the older antecedent population Blood 2005, Hu R. 105,
19 Haemolysis after iron dextran treatment One case report by Niel Hernri (Buus et al, 2007) - a patient developed severe intravascular haemolysis and acute renal failure following intravenous administration of iron dextran. As we known, there was no report about acute haemolylsis in patients with vitamin B12 deficiency after iron dextran administration. Nephrology,dialysis, transplantation, Buus NH 2007,22,661-2
20 conclusion We found a case presented with advanced vitamin B12 deficiency and iron deficiency anemia complicated with acute haemolysis after iron administration and appearance of PNH-like clones, both of which subsided after vitamin B12 administration. Our case Typical PNH
21 The linking of vitamin B12 deficiency and the The linking of vitamin B12 deficiency and the formation of PNH-like clones is intriguing.
22 Thank you for your listening!
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